The Expression Of PKM2 And HIF-lα In Laryngeal Squamous Cell Carcinoma And Its Clinical Indication

Objective: The purpose of this study was to investigate the expression of Pyruvate kinase M2(PKM2) and Hypoxia-inducible factor 1 alpha(HIF-lα) in laryngeal squamous cell carcinoma and to analyze their correlation in laryngeal squamous cell carcinoma. Further, we explored the role of PKM2 and HIF-lα in the process of glycolysis in tumor cells, and thus to provide certain theoretical and experimental basis for the pathogenesis of laryngeal cancer and gene therapy. Methods: Total 37 laryngeal squamous cell carcinoma samples were chosen from the Second Hospital of Hebei Medical University from 2013/5 to 2014/6 which were confirmed by pathology. The patients had received neither chemotherapy nor radiation therapy before surgical excision and 37 adjacent tissues were also studied as controls. The specimens were fixed in 4% paraformaldehyde and paraffin embedded after excision. The expression of PKM2 and HIF-lα in laryngeal squamous cell carcinoma tissues and adjacent tissues were detected by streptavidin peroxidase(SP) immunohistochemical method. The relationship between the expression rate of protein and clinical pathological features were evaluated by Chi-square test. The correlation between PKM2 and HIF-lα in laryngeal cancer were analyzed by Chi-square test and Spearman’s Rank Correlation Analysis. Using SPSS13.0 to analyze the statistical date of experiment, with P<0.05 for a statistical difference. Results: 1 The expression level of PKM2 protein: the rate of PKM2 positive expression in laryngeal carcinoma tissues and adjacent tissues were 62.16% and 13.15%. The difference between the two groups was statistically significant(P<0.01), which indicated expression of PKM2 in laryngeal cancer tissue was significantly higher than adjacent tissues. The rate of PKM2positive expression in medium-poorly differentiated laryngeal squamous cell carcinoma was 85.71%, and 47.83% in well differentiated laryngeal squamous cell carcinoma. The difference between the two groups was statistically significant(P<0.05), indicated PKM2 expression was associated with the degree of pathological differentiation.The rate of PKM2 positive expression in patients with lymph metastasis was 90%, 51.85% in those without lymph metastasis. The difference between the two groups was statistically significant(P<0.05), indicated PKM2 expression was associated with lymphatic metastasis. The rate of PKM2 positive expression in Ⅲ~ Ⅳ stage was 81.82%, 53.85% in Ⅰ~ Ⅱstage. The difference between the two groups was not statistically significant(P>0.05), indicated PKM2 expression has no relationship with clinical stage. The rate of PKM2 positive expression in patients younger than 60 years old was 52.94%, 70% in patients older than 60. The difference between the two groups was not statistically significant(P>0.05), indicated PKM2 expression has no relationship with patients’ age. The rate of PKM2 positive expression in patients who smoked less than or equal to 20 a day was 50%, 65.52% in patients who smoked more than 20 a day. The difference between the two groups was not statistically significant(P>0.05), indicated PKM2 expression has no relationship with smoking.2 The expression level of HIF-lα protein: The rate of HIF-lα positive expression in laryngeal carcinoma tissues and adjacent tissues were 64.86% and 21.62%. The difference between the two groups was statistically significant(P<0.01), indicated HIF-lα expression in laryngeal cancer tissues was significantly higher than adjacent tissues. The rate of HIF-lα positive expression in medium-poorly differentiated laryngeal squamous cell carcinoma was 92.86%, 47.83% in well differentiated laryngeal squamous cell carcinoma. The difference between the two groups was statistically significant(P<0.05), indicated HIF-lα expression was associated with the degree of pathological differentiation. The rate of HIF-lα positive expression in ~ Ⅲ Ⅳ stage was 90.91%, 53.85% in Ⅰ~ Ⅱstage. The difference between the two groups was statistically significant(P<0.05), indicated HIF-lα expression wasassociated with clinical stage. The positive expression rate of HIF-lα in lymphatic metastasis group was 100% and it was 51.85% in no lymphatic metastasis group. The difference between the two groups was statistically significant(P<0.05), indicated HIF-lα expression was associated with lymphatic metastasis. The rate of HIF-lα positive expression in patients younger than 60 years old was 58.82%, 70% in patients older than 60. The difference between the two groups was not statistically significant(P>0.05), indicated HIF-lα expression has no relationship with patients’ age. The rate of HIF-lα positive expression in patients who smoked less than or equal to 20 a day was 62.5%, 65.52% in patients who smoked more than 20 a day. The difference between the two groups was not statistically significant(P>0.05), indicated HIF-lα expression has no relationship with smoking. 3 The correlation between PKM2 and HIF-lα: the expression of PKM2 was positive related with the expression of HIF-lα by Chi-square test and Pearson contingency coefficient of enumeration data(P=0.003<0.01, rs=0.476). Conclusions: 1 The expression of PKM2 and HIF-lα in laryngeal squamous cell carcinoma were higher than adjacent tissues, and the positive expression of PKM2 was related with tumor cells canceration, degree of pathological differentiation and lymphatic metastasis, but not tumor clinical stage and the patients’ age and smoking. The positive expression of HIF-lα was related to tumor cells canceration, degree of pathological differentiation, clinical stage and lymphatic metastasis, but not the patients’ age and smoking. 2 The expression of PKM2 was positive related with HIF-lα in laryngeal squamous cell carcinoma. HIF-lα may raise the glycolysis level of laryngeal cancer tissue through positive feedback loops with PKM2, thus promotes the proliferation, invasion and metastasis of laryngeal squamous cell carcinoma.3 It provides a certain theoretical basis for laryngeal cancer diagnosis and screening to measure the expression of PKM2 and HIF-lα as biological indicators. We can focus on the research of their specific inhibitors asanticancer drug which provides reference for the clinical treatment of laryngeal cancer.